For an introduction, we turn to the Wall Street Journal from September 15, 2015:
President Barack Obama plans to nominate the prominent cardiologist and medical researcher Robert Califf as the next commissioner of the Food and Drug Administration, the White House said Tuesday.
Dr. Califf had been named the FDA’s deputy commissioner for medical products and tobacco—effectively the No. 2 post—in February. He joined the FDA from Duke University, where he had served as a professor of medicine, a leading pharmaceutical researcher and the vice chancellor for clinical and translational research.
The new nomination got some rave reviews. For example, from the WSJ article,
Francis Collins, director of the National Institutes of Health and a scientist who has worked with Dr. Califf for years, called this 'a fantastic nomination.'
Then this in the NY Times (Sept 15, 2015):
'He’s never forgotten that at his core he’s a doctor, and he cares deeply about providing evidence to help people take better care of patients,' said Dr. Robert Harrington, professor and chairman of the department of medicine at the Stanford University School of Medicine, who worked with Dr. Califf at Duke.
Also, a MedPage Today article was entitled, "Califf Nomination for FDA Chief Gets Most High Marks," and included such testimonials as,
'He has a very good understanding of industry and academia, and think that will serve him well,' Caleb Alexander, MD, co-director of the Johns Hopkins Center for Drug Safety and Effectiveness in Baltimore, told MedPage Today....
Also, this from Dr Harlan Krumholz,
He's a broad thinker and a very creative and visionary individual. He will be an outstanding choice.
And this from Dr Sanjay Kaul,
I can't think of a more qualified person than Dr. Califf to lead the FDA at the present time. He is an accomplished leader in cardiovascular disease research whose work has resulted in therapies that save lives and improve the quality of life for millions of patients.Is it time to break out the confetti yet?
Conflicts of Interest a Fly in the Ointment?
The only fly in the ointment was the matter of Dr Califf's ties to industry. The WSJ article included,
Diana Zuckerman, president of the National Center for Health Research, a Washington-based group focusing on medical-product safety, questioned his ties to the drug industry.
'Dr. Califf’s expertise and his close ties to the pharmaceutical industry are both well-known,' she said. 'His ties to industry have been a source of great concern to public-health experts when he was previously considered for FDA commissioner, and those ties raise important questions about this nomination.'
The MedPage Today article noted that Public Citizen's Health Research Group stated,
'During his tenure at Duke University, Califf racked up a long history of extensive financial ties to multiple drug and device companies, including Amgen, Astra-Zeneca, Eli Lilly, Johnson & Johnson, Merck Sharpe & Dohme and Sanofi-Aventis, to name a few,' Michael Carome, MD, the group's director, said in a statement. 'Strikingly, no FDA commissioner has had such close financial relationships with industries regulated by the agency prior to being appointed.'
The MedPage Today article, however, then went on to undermine those concerns, implying that only fringe people like those at Public Citizen were really worried.
Most experts contacted by MedPage Today seemed to think Califf would not have a problem getting Senate confirmation. 'I expect him to be confirmed," said [Dr. Steven] Nissen. 'He is very well liked by people ... in both parties, and I would expect the nomination to go well.'
'All signals suggest that Dr. Califf is well-respected on both sides of the political aisle,' Jay Wolfson, DrPH, JD, senior associate dean at the University of South Florida's Morsani College of Medicine, in Tampa, said in an email.
'There are some who believe his relationship with [the drug industry] may be a problem, but most see it as a value-added factor in building a functional, more streamlined relationship with the industry in order to improve the speed with which truly effective and quality drugs and devices are made available, mitigate the excessive costs associated with pharmaceuticals, and influence policies and practices intended to improve health status.'
Note that the experts were not all named, or their expertise described, the first two paragraphs were really about Dr Califf's political support, and the third paragraph clearly reflected the views of someone who thought that the FDA needs to have a lighter regulatory touch.
There was additional reporting about Dr Califf's conflicts of interest, but again with the effect of minimizing their importance. The Wall Street Journal published a second article on September 18, 2015 which first reported,
From 2009 through early 2015, Dr. Califf received consulting fees of roughly $205,000 from companies including Johnson & Johnson, Merck & Co., GlaxoSmithKline PLC and one medical-device maker, records show. The payments are documented by the federal Open Payments database, and PharmaShine, a database of pharmaceutical disclosures operated by Obsidian Healthcare Disclosure Services LLC. Drug makers spent an additional $21,000 on travel, meals and other expenses for Dr. Califf, data show.
But the article provided this counterpoint,
Kevin Griffis, a spokesman for the Department of Health and Human Services, said Dr. Califf had ceased all work with drug makers once he was hired by the FDA and that he has gone through a rigorous screening process for potential conflicts of interest. Mr. Griffis said Dr. Califf had donated all the consulting fees he has received since the mid-2000s to nonprofit groups.
'Dr. Robert Califf’s professional career has been dedicated to advancing biomedical research, including the rigorous evaluation of the safety, efficacy and appropriate use of both new medical products and those already on the market,' said Mr. Griffis, assistant secretary for public affairs at HHS.
Note that Dr Califf already is at the FDA, in a position that I do not believe required Senate confirmation. It is striking, however, how the agency's own public relations people have jumped to his defense now as a nominee who has to be confirmed by the Senate. However, I suppose that had Dr Califf donated all this fees to a local soup kitchen, they could not be called much of a conflict of interest. But Mr Griffis said "nonprofit groups," without specification, not "soup kitchens." And continue reading to find out more.
A simultaneous NY Times article enlarged a bit on Dr Califf's industry relationships,
He has written scientific papers with pharmaceutical company researchers, and his financial disclosure form last year listed seven drug companies and a device maker that paid him for consulting and six others that partly supported his university salary, including Merck, Novartis and Eli Lilly. A conflict-of-interest section at the end of an article he wrote in the European Heart Journal last year declared financial support from more than 20 companies.
However the NYT article also quoted Mr Griffis about the donations to "nonprofits," and added,
A résumé studded with industry funding is not unusual in academic medicine, Dr. Califf’s supporters note. Doctors are paid consulting fees all the time, and universities routinely conduct clinical trials on behalf of companies. Those contracts help support university researchers’ salaries, a standard practice. Many emphasize that it does not imply an inherent conflict.
His supporters contend that Dr. Califf’s vast experience in the clinical science world could be a major asset in his new post.
Supporters and former colleagues say Dr. Califf’s background makes him perfectly suited to the job of commissioner. He has spent years improving the way clinical trials are conducted, coming up with groundbreaking trial designs for medicines against blood clots.
'His integrity in scientific matters is impeccable, and his innovation in clinical trial design is legendary,' said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, who has been an outspoken critic of both the F.D.A. and drug companies.
Dr. Califf is often in the gym on the StairMaster before 6 a.m., said a former colleague at Duke, Dr. Adrian Hernandez. He often invites younger doctors to join him in golf and has a passion for Duke basketball that he expresses by wearing the team colors on game days.
How could anyone criticize a man who is at the gym at 6 AM?
More seriously, note that while the recent reporting may bring up questions about Dr Califf's conflicts of interest in terms of financial relationships with drug, device and biotechnology companies when he was on the Duke faculty, all the reporting also included passages minimizing the importance of these conflicts. To minimize the issue of conflicts of interest, articles cited unnamed experts, suggesting the logical fallacy of an appeal to authority; noted that the financial ties that were criticized are standard practice in academic health care, suggesting the logical fallacy of an appeal to common practice. The articles also cited Dr Califf's positive attributes which may have been relevant to his work at the FDA, like knowledge of research, but were not related to the question of conflicts of interest. This suggests another appeal to authority, or something of a reverse ad hominem (pro hominem?) fallacy. It seems odd that what appear to be straightforward journalistic reports of a presidential nomination included such attempts to defend the candidate. Note further that many of these logical fallacies appeared not in quotes from Dr Califf's supporters, but in text apparently written by journalists (e.g., "industry funding is not unusual," "in the gym on the Stairmaster," etc.)
Nonetheless, this is the state of play as of this moment. The thrust of the media coverage suggested that Dr Califf is a brilliant physician and researcher, and while he as some ties to industry, they do not amount to much of a problem, except in the eyes of the likes of Public Citizen.
If one digs deeper, however, there is more. When Dr Califf was appointed to his current FDA position in February, 2015, and years earlier when his name was first mentioned as a possible candidate to run the FDA, evidence appeared that his ties to pharmaceutical, biotechnology and device companies were much more serious than what the recent accounts suggested.
Where Does the Money from Industry Sponsored Research Grants Go?
The recent coverage of Dr Califf's nomination in the NY Times dismissed his multiple corporate research grants as common practice. Yet in the TIME coverage of his original appointment to the FDA in February, 2015, this reminder of the significance of corporate sponsored research grants appeared.
Califf says his salary is contractually underwritten in part by several large pharmaceutical companies, including Merck, Bristol-Myers Squibb, Eli Lilly and Novartis.
Note that apologists for physician and academician interaction with industry often claim that industry funding of research grants that does not go directly to individuals does not cause important conflicts of interest. In one sentence, however, this article underlined how these grants support academic salaries, and hence lead to the dependency that is at the heart of conflicted relationships.
As we posted in 2007, academic medical institutions now depend on "external," including corporate research funding to support their research faculty's salaries, and via "overhead," their overall budgets. Dr Lee Goldman, then Dean and Executive Vice President at Columbia University, called faculty who bring in a lot of grant money "tax payers," who earn gratitude, and likely bonuses and perks. Thus Dr Califf's multiple large corporate research grants cannot be completely dismissed as conflicts of interest.
A More Extensive List of Industry Relationships
Furthermore, a relatively obscure February, 2015, report from MDDIOnline noted that Dr Califf had more industry relationships than were reported this month,
Conflict of interest disclosures dating back to 2007 made public by the DCRI show that Califf has been paid for consulting or other services provided to a number of medical device pharmaceutical, and biotech companies, including Medtronic, Acumed, Bayer Healthcare, Merck, Novartis, Roche, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly & Co. Califf also disclosed that he held equity in two pharmaceutical companies—Boulder-based N30 Pharmaceuticals and South San Francisco, CA-based Portola Pharmaceuticals—as recently as 2014. Califf retired from Portola’s board of directors January 26, according to a press release from the company.A somewhat more obscure commentary by Martha Rosenberg in OpEdNews provided even more extensive listings of Dr Califf's industry relationships. And it suggested having a look at the disclosures he has made in the past in medical journal articles. A statement in a 2013 JAMA commentary was particularly telling,
Dr Califf receives research grants that partially support his salary from Amylin, Johnson & Johnson, Scios, Merck/Schering-Plough, Schering-Plough Research Institute, Novartis Pharma, Bristol-Myers Squibb Foundation, Aterovax, Bayer, Roche, and Lilly; all grants are paid to Duke University. Dr Califf also consults for TheHeart.org, Johnson & Johnson, Scios, Kowa Research Institute, Nile, Parkview, Orexigen Therapeutics, Pozen, WebMD, Bristol-Myers Squibb Foundation, AstraZeneca, Bayer/Ortho-McNeil, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GlaxoSmithKline, Li Ka Shing Knowledge Institute, Medtronic, Merck, Novartis, sanofi-aventis, XOMA, University of Florida, Pfizer, Roche, Servier International, DSI-Lilly, Janssen R&D, CV Sight, Regeneron, and Gambro; all income from these consultancies is donated to nonprofit organizations, with most going to the clinical research fellowship fund of the Duke Clinical Research Institute. Dr Califf holds equity in Nitrox LLC, N30 Pharma, and Portola.
These lists of corporations from which Dr Califf got salary support and consulting fees are much longer than previous lists. He acknowledged 13 commercial research sponsors, and consulted for 32 organizations, most of which were pharmaceutical companies. Again, given that the salary support and overhead likely supplied by corporate research grants do suggest conflicts of interest, Dr Califf may have had many more of these sorts of conflicts than current reports implied
A Seat on a Pharmaceutical Company Board of Directors
Note that the MDDIOnline article mentioned that Dr Califf was a member of the board of directors of Portola Pharmaceuticals. That was a significant source of income. According to the Portola Pharmaceuticals 2015 proxy statement, Dr Califf received $259,623 in cash and stock options from the company in 2014. I cannot find anything to suggest that this payment did not go directly to him. This position, and the money it paid were not mentioned in the recent coverage. That payment alone seems to represent a major conflict of interest.
However, being on the board of directors of a health care corporation presents a deeper conflict than that produced by a simple payment of money or stock options, no matter how large. In 2006, we discussed corporate directorships as a new and important species of conflict of interest for medical academics. As we have previously posted, corporate directors have fiduciary responsibilities to the company and its shareholders to support its financial success. They are supposed to "demonstrate unyielding loyalty to the company's shareholders" [Per Monks RAG, Minow N. Corporate Governance, 3rd edition. Malden, MA: Blackwell Publishing, 2004. P.200.] Thus corporate directors have a much more significant commitment to the corporation than do corporate consultants, or researchers supported by corporate grants.
Where Did Those Donated Consulting Payments Go?
Also note that the disclosure statement in the JAMA article mentioned that most of the consulting payments Dr Califf received went to the clinical research fellowship of the Duke Clinical Research Institute (DCRI). Dr Califf was the first director of DCRI,
So, while Dr Califf apparently did donate the consulting fees to a non-profit organization, that organization actually was part of Duke, and an organization that Dr Califf once led. It appears likely that Dr Califf benefited at least indirectly in terms of institutional gratitude and reputation from these consulting fees that he donated to his own institution. So it appears that Dr Califf's donations of his consulting fees did not reduce the conflicts of interest generated by these fees to the extent suggested by the current FDA spokesperson and current media reports.
Payments for "Educational Activities"
Finally, perusal of disclosures of Dr Califf's commercial relationships made by the Duke Clinical Research Institute for the years 2010-2015 showed that he received payments for "educational activities" in 2011 from Amylin. Information about earlier years is not available on this site, but in 2009, Dr Daniel Carlat wrote this about Dr Califf's then rumored candidacy for leadership of the FDA in the Carlat Psychiatry Blog,
look at these industry disclosures. He took money—lots of money--from 18 different pharmaceutical or device firms. Most of this was not for research, but for consulting and speaking, including CME. If Dr. Califf believes that it is ethical for physicians to help drug companies market their products, that’s his own business. But to elevate him to a position in which he is the country’s chief watchdog over unsafe medications and foods seems a dangerous move. With money from 18 drug companies padding his bank account, he will presumably spend most of his FDA career recusing himself from crucial decisions. Not a good idea.
There has been no mention of Dr Califf being a paid speaker for pharmaceutical companies in any of the recent reporting. Dr Carlat implied that Dr Califf was paid to speak to further marketing objectives of pharmaceutical companies, that is, was giving "drug talks." Since the publication of "Dr Drug Rep" in the New York Times in 2007, authored by Dr Carlat, the public has learned that such talks mainly include content provided by the pharmaceutical companies, and are meant by the companies as marketing exercises. From that case we also learned that physicians who deviate from the marketing message do not last long on speakers' bureaus. (See posts here and here.)
Paid speakers may be regarded by pharmaceutical companies as paid "key opinion leaders," KOLs, who serve a marketing function in the guise of academics. As noted here and here, the companies buying their services may believe they have bought the services of sales people. Evidence about key opinion leaders actually performing like marketers has come from documents revealed during litigation (e.g., see this recent example of a huge monetary settlement made of charges that GlaxoSmithKline, a major multinational drug company committed fraud among other things, and in the course of its unethical activities used key opinion leaders as marketers). Also, see the Neurontin marketing plan (see post here), and the Lexapro marketing plan (see post here) for examples of how company keaders view key opinion leaders as marketers.
So the revelation that Dr Califf received corporate payments for "education" suggests a bigger commitment to corporate marketing objectives than has previously been revealed.
So, looking at not only current media reports, but media reports from earlier this year, and also proxy statements, the fine print of journal articles, and old blog posts, it appears that Dr Robert Califf really did have very substantial financial interactions with the drug, device and biotechnology industry. These interactions likely underwrote his salary and his standing with the leaders of his former employer, Duke University. Dr Califf seemed to be a paid speaker for drug companies on at least two occasions, suggesting that the companies may have put him in a covert marketing role, or viewed him as a paid key opinion leader. Finally, Dr Califf served on the board of directors of one drug company, a much deeper commitment than being a sponsored researcher or consultant.
Thus Dr Califf really appears to be one of the most, if not the most drug, device and biotechnology industry connected individual ever nominated to lead the agency that is the most important regulator of the US drug, device and biotechnology industry. Some of his connections, particularly his previous membership on a pharmaceutical company board, and his previous roles as a paid pharmaceutical speaker, suggested not only financial relationships, but commitments to companies' financial and marketing goals. These appear to be major conflicts of interest vis a vis Dr Califf's current leadership position at the FDA, and his nomination to be the ultimate leader of this regulatory agency. This is the revolving door writ large.
As we have said very recently, the revolving door can be veiwed as a species of conflict of interest. Government officials who can look forward to extremely lucrative employment in health care industry may be much more inclined to seem friendly to the industry while in office. Government officials who just came from industry are likely to maintain their industry mindset and be mindful of their industry friends.
Worse, some experts have suggested that the revolving door is in fact corruption. As we noted here, the experts from the distinguished European anti-corruption group U4 wrote,
The literature makes clear that the revolving door process is a source of valuable political connections for private firms. But it generates corruption risks and has strong distortionary effects on the economy, especially when this power is concentrated within a few firms.Furthermore, the ongoing and increasing revolving door phenomenon clearly suggests excess coziness between industry and government, now to the extent that industry and government leaders of health care are becoming interchangeable. This suggests that health care is increasingly run by this cozy ingroup, who very likely put their own interests ahead of those of patients and the public.
The continuing egregiousness of the revolving door in health care shows how health care leadership can play mutually beneficial games, regardless of the their effects on patients' and the public's health. Once again, true health care reform would cut the ties between government and corporate leaders and their cronies that have lead to government of, for and by corporate executives rather than the people at large.
ADDENDUM (28 September, 2015) - This post has been republished on the Naked Capitalism blog, and OpEdNews.
ADDENDUM (28 September, 2015) - See also more detail on Dr Califf's activities on the Portola board on the PEU Report blog.